The overall objective of the proposed research is to study the functional behavior of normal, abnormal human hemoglobins and some other mammalian hemoglobins, with particular emphasis on the mechanism of ligation reactions. Human variants: Hb Sydney Val E11 (G7) yields Ala; Hb Zurich His beta (63) yields Arg; Hb Hammersmith beta (42) Phe yields Ser; Hb Byrn Mawr Phe beta (85) yields Ser; fetal hemoglobins (fI, FII); the minor components of normal adult hemoglobin (AIa, AIb, AIc) and cat hemoglobins have been selected for the present study. The stepwise dissociation kinetics of ligand dissociation from carboxy and nitrosylhemoglobins have been studied. Studies on cat and rabbit hemoglobins and human hemoglobin variants are in progress.